Fig. 6: Endothelial-specific deletion of Nogo-B improves metabolic and vascular dysfunction. | Nature Communications

Fig. 6: Endothelial-specific deletion of Nogo-B improves metabolic and vascular dysfunction.

From: Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases

Fig. 6

A Schematic representation of the experimental design. Metabolic and vascular functions were assessed in Nogo-A/Bf/f or Nogo-A/BECKO mice fed with SD or HFD for 6 months (Created in BioRender. Di Lorenzo, A. (2025) https://BioRender.com/i50g226). B Body weight (Nogo-A/Bf/f HFD n = 8 mice and Nogo-A/BECKO HFD n = 10 mice). C GTT (Nogo-A/Bf/f HFD n = 15 mice and Nogo-A/BECKO HFD n = 17 mice). D ITT (Nogo-A/Bf/f HFD n = 8 mice and Nogo-A/BECKO HFD n = 10 mice). E PTT (Nogo-A/Bf/f HFD n = 8 mice and Nogo-A/BECKO HFD n = 8 mice). F SBP, G DBP, and H MBP measured by radiotelemetry as described in Methods (Nogo-A/Bf/f SD n = 5 mice, Nogo-A/BECKO SD n = 5 mice, Nogo-A/Bf/f HFD n = 7 mice and Nogo-A/BECKO HFD n = 5 mice). I, J PE-induced vasoconstriction (Nogo-A/Bf/f SD n = 8 mice, Nogo-A/BECKO SD n = 10 mice, Nogo-A/Bf/f HFD n = 4 mice and Nogo-A/BECKO HFD n = 5 mice). K, L Myogenic tone (Nogo-A/Bf/f SD n = 8 mice, Nogo-A/Bf/f HFD n = 4 mice, Nogo-A/BECKO SD n = 5 mice and Nogo-A/BECKO HFD n = 7 mice). M, N Ach-mediated vasodilation (Nogo-A/Bf/f SD n = 11 mice, Nogo-A/BECKO SD n = 10 mice, Nogo-A/Bf/f HFD n = 7 mice and Nogo-A/BECKO HFD n = 8 mice); O, P flow-induced vasodilation (Nogo-A/Bf/f SD n = 7 mice, Nogo-A/BECKO SD n = 8 mice, Nogo-A/Bf/f HFD n = 6 mice and Nogo-A/BECKO HFD n = 8 mice), and Q flow-induced vasodilation after myriocin treatment (1 mg/kg, i.v., o.n.), (n = 3 mice per group). LC–MS/MS quantification of R total and S specific Cer, C16:0-dihydroceramide (dhC16:0-Cer), dihydrosphingosine (dhSph), sphingosine (Sph), sphingosine-1-phosphate (S1P), and T total and U specific SM in EC FACS-sorted from heart and lung of Nogo-A/B-deficient and WT mice fed with HFD for 6 months. Data are expressed relative to WT HFD (Nogo-A/Bf/f HFD n = 18 mice and Nogo-A/BECKO HFD n = 17 mice). V Heatmap of gene for the SPT complex, inflammation, and lipid transport in FACS-sorted EC from heart and lung, *indicates significant differences (Nogo-A/Bf/f HFD n = 4 mice and Nogo-A/BECKO HFD n = 4 mice). Data were expressed as mean ± SEM. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001. Statistical analysis was performed with two-way ANOVA with Sidak multiple comparisons test (B, C, D, E, I–Q), one-way ANOVA (F–H) unpaired t-test two-tailed (R–U). Source data are provided as a Source Data file.

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